This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There is converging evidence that abnormal cortical connectivity may be an important factor in the pathophysiology of schizophrenia. Supporting data have come from studies of schizophrenia, with reports of decreased neuropil, aberrant cell migration, abnormal correlations between volumes of different cortical regions, and altered activation patterns from PET studies. Although white matter provides the physical foundation for cortical connectivity, there has been little in vivo study of white matter, perhaps because of lack of appropriate tools. Diffusion Tensor Imaging (DTI) is a magnetic resonance imaging (MRI) method which is uniquely suited to the study of white matter because it can be used to quanitify the magnitude and directionality of tissue water mobility (i.e., self-diffusion) in three dimensions. Structures in white matter (WM), such as myelin sheaths, axon membranes, cytoskeletal elements and white matter tracts, can act as barriers to water mobility, causing water molecules to move farther along paths that are parallel to fibers rather than those that are perpendicular to these fibers. When there is a directional dependence of water mobility, the diffusion is described as being anisotropic. The anisotropy can be quantified and used to assess the microstructural organization of white matter fibers. Highly regular, organized fibers will have high anisotropy;less well-organized fibers will have lower anisotropy measures. In a preliminary study of 10 chronic schizophrenic subjects (SZ) and 10 normal controls (NC), we used DTI to assess white matter fractional anisotropy (FA). The white matter FA was found to be significantly reduced in schizophrenic subjects (Lim et all 1999). This finding suggests that white matter microstructure organization is altered in schizophrenia, providing further evidence of compromised cortical connectivity. In this application, we propose to study schizophrenia patients and normal controls with MRI and neurocognitive assessments, expanding the scope from our preliminary study. Specifically, our aims are to: 1) Replicate our initial finding of decreased white matter fractional anisotropy (FA) with a new group of schizophrenic (SZ) patients and normal controls (NC). Our hypotheses are: A) As a group, SZ will have different white matter FA than NC. We anticipate the FA in SZ to be lower. B) For the SZ, white matter FA will vary by region with greatest abnormality in the prenatal region. 2) Examine the neurocognitive correlates of white matter FA in schizophrenia. Measures will include five neucognitive domains derived from a neurocognitive battery. Our hypothesis is that within the SZ group, FA from selected white matter regions will be correlated with specific neurocognitive domains.